title: Liver tumors induced in B6C3F1 mice by 7-chlorobenz[a]anthracene and 7-bromobenz[a]anthracene contain K-ras protooncogene mutations.
abstract: We previously examined the tumorigenicity of 7-chlorobenz[a]anthracene (7-Cl-BA) and 7-bromobenz[a]anthracene (7-Br-BA) in the neonatal mouse bioassay and found that 7-Cl-BA and 7-Br-BA induced hepatocellular adenoma in 92 and 96% of the mice and hepatocellular carcinoma in 100 and 83% of the mice, respectively. In the present study, mRNA was isolated from each of the liver tumors induced by the two compounds and reverse-transcribed to cDNA. Portions of the K- and H-ras oncogene coding sequences were then amplified and analyzed for DNA sequence alterations. Eighty-three percent (20/24) of 7-Cl-BA-induced and 91% (20/22) of 7-Br-BA-induced liver tumors had activated ras protooncogenes. In contrast to the general finding of H-ras mutations in B6C3F1 mouse liver tumors, both compounds had 95% (19/20) of the mutations located at the first base of K-ras codon 13, resulting in a pattern of GGC --> CGC. Thus, our results demonstrate that 7-Cl-BA and 7-Br-BA induce a unique type of ras (K-ras) oncogene activation in liver tumors of B6C3F1 mice.
authors.affiliation: National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Xia
authors.forename: P
authors.initials: P
authors.lastname: Yi
authors.forename: D J
authors.initials: DJ
authors.lastname: Zhan
authors.forename: L S
authors.initials: LS
authors.lastname: Von Tungeln
authors.forename: R W
authors.initials: RW
authors.lastname: Hart
authors.forename: R H
authors.initials: RH
authors.lastname: Heflich
authors.forename: P P
authors.initials: PP
authors.lastname: Fu
mesh_terms: D018248:Adenoma, Liver Cell / Q000139:chemically induced / Q000235:genetics*; D000818:Animals; D000873:Anthracenes; D001551:Benz(a)Anthracenes; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics*; D011905:Genes, ras; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D017354:Point Mutation; D012334:RNA, Neoplasm / Q000235:genetics
chemical_list: D000873:Anthracenes; D001551:Benz(a)Anthracenes; D002273:Carcinogens; D012334:RNA, Neoplasm; C046094:7-chlorobenz(a)anthracene; C038901:7-bromobenzanthracene